Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed clinicopathological studies on early-onset sepsis (5 infants, less than 72 hours of life, EOS) and late-onset sepsis (15 infants, greater than 72 hours, LOS) of very low birth weight, less than 1500 g (VLBW). In EOS, the clinical features mimic the respiratory distress syndrome and hematological changes were not observed. The lungs showed slight interstitial pneumonia with structural immaturity, hyaline membranes, hemorrhage, and minimal infiltration by polymorphonuclear neutrophils (PMNs). The pathogen was group B streptococcus or weakly gram-negative bacilli. In LOS, pneumonia proceeded to sepsis and neutropenia with elevated numbers of circulating immature neutrophils, and increased levels of C-reactive protein were observed at the onset of sepsis. Severe pneumonia with infiltration of numerous PMNs and bacterial colonies and polymicrobial infection by nosocomial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were common. The thymus and spleen weights varied but retained normal structure in EOS. The thymus was depleted of lymphocytes, and the spleen was hypertrophic but poorly reactive against infection in LOS. The pathogenesis of EOS is regarded as being more closely correlated with lung immaturity and circulatory disorder in early life, whereas that of LOS is associated with immunological defenses of the host, potency of the pathogens, and terminal multiple organ failure.
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PMID:Clinicopathological differences between early-onset and late-onset sepsis and pneumonia in very low birth weight infants. 223 61

Neonatal host defense simulates a clinical state of immunodeficiency that predisposes the preterm and term newborn to overwhelming bacterial sepsis. There are various immunologic components that are deficient in the newborn and new methods to enhance their function. Defects in both the quantitative and qualitative aspects of the neonatal phagocyte contribute substantially to the immaturity of neonates' immune systems. The neonate lacks an adequate number of granulocyte bone marrow progenitor cells, and has a decreased neutrophil storage pool and an increased tendency to peripheral neutropenia during neonatal sepsis. Additionally, the neonatal granulocyte demonstrates altered physiologic function compared with that found in the adult with respect to chemotaxis, phagocytosis, oxidative metabolism, and bacterial killing. Some recent clinical studies have suggested the benefit of using adult neutrophil transfusions as adjuvant treatment during neonatal bacterial sepsis, yet other studies have found the use of polymorphonuclear neutrophil leukocyte transfusions to be inconclusive. Reduced circulating immunoglobulins and impaired production of specific antibody have also led to recent trials in the use of prophylactic intravenous immunoglobulin in preterm infants predisposed to sepsis. Recently, hematopoietic colony-stimulating factors have been demonstrated to improve in vitro neonatal neutrophil physiologic activity. Future therapy of neonatal sepsis will depend on new nontoxic methods for enhancing neonatal host defense.
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PMID:Neonatal neutrophil host defense. Prospects for immunologic enhancement during neonatal sepsis. 264 45

Neonatal host defense simulates a clinical state of immunodeficiency that predisposes the preterm and term newborn to overwhelming bacterial sepsis. Defects in both the quantitative and the qualitative aspects of the neonatal phagocyte contribute significantly to the immaturity of their immune system. The neonate lacks adequate numbers of granulocyte bone marrow progenitor cells and has a decreased neutrophil storage pool and an increased tendency to peripheral neutropenia during neonatal sepsis. Additionally, the neonatal granulocyte demonstrates altered physiological function compared with that found in the adult with respect to chemotaxis, phagocytosis, oxidative metabolism, and bacterial killing. Reduced circulating immunoglobulins and impaired production of specific antibody are additional hallmarks of altered neonatal immunity. The use of adult neutrophil transfusions for the treatment of neonatal sepsis has shown promise in some clinical studies and no difference in others. Recent investigations have examined the use of intravenous gamma-globulin for prophylaxis and treatment of neonatal sepsis. The following review summarizes the state of immunodeficiency in the newborn and the potential role of polymorphonuclear leukocyte transfusions in the treatment of overwhelming neonatal bacterial sepsis.
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PMID:Neutrophil transfusions in the treatment of neonatal sepsis. 266 51

Studies on proliferation and differentiation of granulocyte-monocyte progenitor cells in Chediak-Higashi syndrome (CHS) were done on a 1-month-old patient, using the soft-agar bone marrow culture technique. The number of granulocyte-macrophage colony-forming cells (GM-CFC) was markedly increased, but with a normal distribution into granulocyte, macrophage, or mixed colonies. Morphologic, cytochemical, and ultrastructural studies showed that 70% of the colonies consisted of cells with giant lysosomes typical of CHS, and in the remaining 30% abnormal cells were not detected. The supply of granulocyte-macrophage colony-stimulating factor (GM-CSF) by the patient's peripheral blood leukocytes was markedly decreased. Inhibition of normal in vitro granulopoiesis by the patient's lymphocytes or serum was not demonstrated. It appears that granulocyte progenitors in CHS proliferate normally, or even in excess, probably in response to intramedullary destruction of granulocytes. The majority of the progenitors are intrinsically defective and give rise to colonies that contain the abnormality. In others the defects are unidentifiable, probably due to the immaturity of the specific fusion process of the cytoplasmic granules. The abnormal leukocytes in CHS are also defective in their capacity to provide GM-CSF, and this may account in part to the overt neutropenia. These studies demonstrate that the basic cytoplasmic abnormalities of the granulocytes and monocytes in CHS are embedded in the granulocytic-monocytic committed stem cell.
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PMID:Chediak-Higashi syndrome. Expression of the cytoplasmic defect by in vitro cultures of bone marrow progenitors. 374 Mar 66

Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG-CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.
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PMID:A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. 752 Jul 70

To extend our studies about phenotypical and functional alterations of G-CSF-induced neutrophils we have evaluated their light-scatter profile, mobilization of intracellular calcium ([Ca2+]i) and membrane depolarization after stimulation. A significant increase in the forward scatter signals could be demonstrated in such neutrophils from patients with neutropenias of various origin and from healthy test subjects. This increase began 4 h and returned to normal 96 h after G-CSF injection in the latter group. We found an impairment of [Ca2+]i mobilization in neutrophils from patients with glycogen storage disease type IB after stimulation of these cells with fMLP. It was even more pronounced than in severe congenital neutropenia (SCN). However, [Ca2+]i fluxes were normal when ionomycin was used. Neutrophils from patients with cyclic neutropenia (cyNP) and chemotherapy-induced neutropenia (chNP) mobilized [Ca2+]i similar to those from healthy donors. Furthermore, we found a decreased percentage of neutrophils depolarizing after stimulation with fMLP and PMA in patients with SCN, whereas membrane depolarization was normal in patients with chNP and cyNP. All the alterations found here are suggested to be caused by a partial immaturity of the neutrophils, although in vivo activation and a direct effect of G-CSF on myeloid precursors might be involved.
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PMID:Changes in light-scatter profile, membrane depolarization and calcium mobilization of neutrophils induced by G-CSF in vivo. 752 31

Therapy with myeloid colony-stimulating factors has been safely and effectively used in a wide variety of situations associated with neutropenia. We present a case of pseudoleukemia occurring in a patient with lymphoma and pancytopenia after 2 days of treatment with granulocyte colony-stimulating factor (G-CSF). Bone marrow aspirate and flow cytometry study results were consistent with acute myelomonocytic leukemia but were normal after G-CSF was discontinued for 4 days. As previous phase I studies of bone marrow morphology after G-CSF use have not described the extreme myeloid immaturity seen in this patient, it seems likely that the action of G-CSF was enhanced by factors associated with the patient's illness. We emphasize the clinical importance of this case in light of the widespread use of G-CSF.
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PMID:Pseudoleukemia after granulocyte colony-stimulating factor therapy. 753 47

A nineteen-year-old woman whose Hodgkin's disease had relapsed experienced acral erythema in association with a asymptomatic pericardial friction rub following autologous bone marrow transplantation. An echocardiogram revealed a large pericardial and right pleural effusion. Since blood cultures gave negative results, renal function was normal, and the patient had neither neutropenia nor elevated temperature, an infectious cause was deemed unlikely and invasive procedures were not performed. These effusions resolved spontaneously. We propose that this patient's acral erythema and associated pericardial and pleural inflammation represent cutaneous and serosal toxic reactions to high-dosage chemotherapy that occur with the onset of leukocyte recovery. If so, acral erythema may signal the beginning of a toxic drug reaction. The appearance of erythema associated with lymphocyte recovery is due to immune hypersensitivity secondary to immaturity of the reconstituting immune system. Thus, we recommend that patients with acral erythema be examined for pleuropericarditis, especially if they experience chest pain.
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PMID:Pericarditis associated with acral erythema of chemotherapy: a syndrome of cutaneous and serosal toxicities? 840 22

The minimal acute inflammatory response to tissue injury is one of the most dramatic differences between fetal and adult wound healing. Considering the prominent role of inflammation in adult tissue repair, this study tested the hypothesis that the minimal fetal inflammatory response to tissue injury plays a central role in the "scarless" fetal repair process. Sponge implants were treated with lethally irradiated or live bacteria and placed subcutaneously in fetal rabbits to test the ability of the fetus to mount an acute inflammatory response to bacterial antigens present at the wound site and to analyze the effects of this inflammatory response on fetal fibroplasia and neovascularization. After harvest, these implants were examined histologically for inflammation, fibroblast infiltration, collagen deposition, and neovascularization, and collagen deposition was measured using hydroxyproline quantitation by high-performance liquid chromatography. Bacteria-treated implants showed dose-dependent acute inflammatory responses and significant increases in collagen deposition compared with control sponges. Implants containing live bacteria demonstrated maximal fibroplasia and neovascularization. These findings suggest that, despite neutropenia and immaturity of the fetal immune system, the fetus is capable of mounting an acute inflammatory response to avirulent bacteria present at the wound site. Fetal inflammatory cells which respond to this bacterial stimulus appear capable of initiating an adult-like healing response. Thus, by failing to provide a bacterial stimulus for leukocyte recruitment at the site of tissue injury, the sterile fetal environment appears to play a role in effecting "scarless" fetal wound healing.
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PMID:Biology of fetal repair: the presence of bacteria in fetal wounds induces an adult-like healing response. 846 58

The immaturity of neonatal phagocytic immunity contributes to increased mortality during neonatal sepsis. Neonates have both quantitative and qualitative neutrophil defects with decreased bone marrow neutrophil storage pool (NSP) reserves, an inability to increase neutrophil production, and defective neutrophil functional activity. Neonates respond to overwhelming sepsis with depletion of the NSP and the development of peripheral neutropenia. The myelopoietic cytokines granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been documented to induce neutrophilia in neonatal animals and human infants, increase the NSP, and upregulate neutrophils for improved functional activity. Preclinical studies in neonatal rats demonstrate increased survival with prophylactic G-CSF during experimental group B streptococcal sepsis. In pilot phase I/II human trials, G-CSF and GM-CSF were demonstrated to be both safe and well tolerated and to induce significant increases in absolute neutrophil count and NSP. Prophylactic GM-CSF in the very low birth weight neonate may reduce the incidence of nosocomial infections. Phase III trials are needed to further delineate the clinical usefulness of these myelopoietic cytokines in neonates with a high predisposition to sepsis.
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PMID:Potential use of granulocyte colon-stimulating factor and granulocyte-macrophage colony-stimulating factor in neonates. 966 63


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